16‐SS1 Case 1 V Paradis Pathology Dpt, Beaujon hospital Clichy, France
43 year‐old man Alcohol consumption (50 g/day) for 5 years Presented jaundice and ascitis Liver function tests o PT 35%, AST 105 IU/ml, ALT 52 IU/ml, total Bil. 440 µM/l, Alk. P 149 IU/ml, GGT 212 IU/ml o Maddrey score (45) Suspicion of cirrhosis with Acute Alcoholic Hepatitis (AAH) o Corticoids 40 mg/day for 7 days During treatment, he presented digestive hemorrhage & Acute renal insufficiency A transjugular biopsy was performed
20 mm
Advanced fibrosis (pericellular ++) with Acute Alcoholic Hepatitis (no steatosis)
PT ➘ (15%), Creatinin ➚ AST 107 IU/ml, ALT 133 IU/ml, t.bil 550 µmol/l, c.bil 370 µmol/l, Alk. P 123 IU/ml, GGT 282 IU/ml MELD 40 Liver transplantation (5 days after liver biopsy)
1800 g
Clinical entity encompassing an acute deterioration of liver function in patients with underlying chronic liver disease or cirrhosis , which results in failure of one or more organs and high short‐term mortality ☞ Heterogeneity of definition (Up to 13 definitions published) ☞ Prevalence: 25 to 40% of cirrhotic patients admitted to the hospital ☞ Mostly Viral and/or OH chronic liver disease ☞ Triggers: Bacterial infections, OH, Viral relapse, Unknown (20‐45%) ☞ Organ failure (SOFA: Sequential Organ Failure Assessment) : Kidney (56%) > Liver > Coagulation > Brain > Circulation> Lung (9%) Hernaez R et al Gut 2017 (review)
Aims Characterize the liver histological features in ACLF Investigate whether histological parameters can determine the prognosis and differentiate end‐stage fibrotic liver disease from ACLF Study whether etiology influences histology–prognosis relationship Rastogi A et al Virchows Arch 2011
Rastogi A et al Virchows Arch 2011
LB helpful for (1) Prognostication, (2) Differentiation acute liver failure from acute‐on‐chronic liver failure, (3) providing clues to the underlying etiology (might influence treatment strategy) Rastogi A et al Virchows Arch 2011
Required in settings of Diagnostic uncertainty and/or concurrent liver disease Determine the accurate staging of ALD May help to evaluate the prognosis in alcoholic hepatitis
CK8/CK18 Assess the value of early liver biopsy in patients with acute deterioration of alcoholic cirrhosis diagnose ASH grade the severity of ASH determine its prognostic value Liver biopsy performed between days 1 and 7 of admission Review by 2 pathologists Score 0 1 2 3 4 5 Ballooned 0% <5% 5‐10% 10‐20% 20‐50% >50% hepatocytes Lobular Infl 0 0‐1 0‐1 1 1 1‐2 Grade ASH 0 1 2 Mookerjee RP J Hepatol 2011
Fibrosis Disagreement in >30% of cases Cirrhosis (75%) over the definition of hepatocyte Incomplete cirrhosis (16%) ballooning Indeterminate cirrhosis (9%) Steatosis K8/18 immunostaining, facilitated mutual agreement by the No (31%) & Mild (36%) pathologists on Ballooning item Moderate (17%) Marked (16%) The score loss of K8/18 staining ASH grading system (indication of ballooning Grade 0 / absent (54%) degeneration) was correlated Grade 1 / mild‐moderate (21%) with ASH grading (r = 0.7, p <0.0001) Grade 2 / severe (25%) Mookerjee RP J Hepatol 2011
ASH grade correlated with survival (p<0.001) Mookerjee RP J Hepatol 2011
Altamirano J Gastro 2014
Altamirano J Gastro 2014
16SS1 Case 1 +3 +2 0 +2 TOTAL 7 52% of survival @ 3 months
7 centers (2006‐2010) Case control study 26 severe AH failed to response to therapy (mean Lille model 0.88) 26 matched controls Follow‐up 3 resumed drinking OH o @720, 740 and 1140 days Mathurin P NEJM 2011
3 years later: ALT 3N, GGT 5N, no metabolic syndrome
ACLF Syndrome characterized by acute and severe hepatic abnormalities in patients with underlying chronic liver disease or cirrhosis In contrast to decompensated cirrhosis, ACLF has a high short‐term mortality , mimicking the prognosis of acute liver failure Concerns mostly Viral and/or alcohol chronic liver diseases Liver histology is a good predictor of outcome o Stage of fibrosis (>F3), extent of ductular reaction, ballooning , apoptosis and parenchyma left are independent pronostic factors Alcoholic Liver disease o Liver histology is performant for diagnosis and prognosis
Dead Sea, October 14, 2018
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